Reconstructing the value puzzle in health technology assessment: a pragmatic review to determine which modelling methods can account for additional value elements.

Health technology assessment (HTA) has traditionally relied on cost-effectiveness analysis (CEA) as a cornerstone of evaluation of new therapies, assessing the clinical validity and utility, the efficacy, and the cost-effectiveness of new interventions. The current format of cost-effectiveness analysis, however, does not allow for inclusion of more holistic aspects of health and, therefore, value elements for new technologies such as the impact on patients and society beyond its pure clinical and economic value. This study aimed to review the recent modelling attempts to expand the traditional cost-effectiveness analysis approach by incorporating additional elements of value in health technology assessment. A pragmatic literature review was conducted for articles published between 2012 and 2022 reporting cost-effectiveness analysis including value aspects beyond the clinical and cost-effectiveness estimates; searches identified 13 articles that were eligible for inclusion. These expanded modelling approaches mainly focused on integrating the impact of societal values and health equity in cost-effectiveness analysis, both of which were championed as important aspects of health technology assessment that should be incorporated into future technology assessments. The reviewed cost-effectiveness analysis methods included modification of the current cost-effectiveness analysis methodology (distributional cost-effectiveness analysis, augmented cost-effectiveness analysis, extended cost-effectiveness analysis) or the use of multi-criteria decision analysis. Of these approaches, augmented cost-effectiveness analysis appears to have the most potential by expanding traditional aspects of value, as it uses techniques already familiar to health technology assessment agencies but also allows space for incorporation of qualitative aspects of a product's value. This review showcases that methods to unravel additional value elements for technology assessment exist, therefore, patient access to promising technologies can be improved by moving the discussion from "if" to "how" additional value elements can inform decision-making.

Dry eye disease ranking among common reasons for seeking eye care in a large US claims database.

OBJECTIVES: Dry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care. METHODS: In this population-based study using the US Department of Defense Military Health System claims database of >9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003-2015) and annual incidence (2008-2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions. RESULTS: In 2003-2015, the most common ocular conditions were disorders of refraction and accommodation (25.84%), cataracts (17.14%), glaucoma (7.27%), disorders of the conjunctiva (6.76%), other retinal disorders (5.94%), and DED (5.28%). DED was the fifth most prevalent ocular condition in women (7.78%) and ninth most prevalent in men (2.96%). In 2012, DED had the third highest annual incidence (0.87%), behind disorders of refraction/accommodation (1.87%) and cataracts (1.50%). CONCLUSION: This study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment.

A State Transition Model for Health Outcomes Associated with Vorapaxar Treatment as an Add-on to Standard Care Antiplatelet Therapy in the Prevention of Thrombotic Events for Patients with a Recent Myocardial Infarction.

BACKGROUND: The TRA 2°P-TIMI 50 trial showed the addition of vorapaxar to standard care (SC) antiplatelet therapy reduced the combined risk of death, myocardial infarction (MI), and stroke, while exhibiting an increase in moderate, but not other bleeding events. OBJECTIVE: Our objective was to estimate the long-term health benefits and risks of vorapaxar as an add-on to SC treatment (lifetime aspirin and up to 12 months of clopidogrel) for patients with a prior MI and without a history of cerebrovascular disease. METHODS: In the state transition model we developed, the patients transition between states due to recurrent MI, stroke, or death, and are at risk of non-fatal bleeding. Risk equations were developed from individual patient-level data from the TRA 2°P-TIMI 50 trial to predict long-term cardiovascular (CV) outcomes. Additional sources informed inputs for case fatality, bleeding rates on SC, risk of non-CV death, and utilities. RESULTS: Over a lifetime horizon, fewer CV events and more bleeding events occurred in the vorapaxar (VOR) + SC arm, relative to the SC-only arm. These results were ultimately accompanied by an increase in life expectancy and health benefits associated with add-on vorapaxar treatment, as the VOR + SC arm yielded an average of 8.27 discounted quality-adjusted life-years (QALYs) compared with an average of 7.96 discounted QALYs in the SC-only arm. CONCLUSION: This model framework leveraged novel risk equations to make long-term projections of CV events in a population at high risk of recurrence. Model results suggest vorapaxar is most effective as add-on therapy to SC antiplatelet treatment when initiated upon hospital discharge post-MI.

Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.

Meta-analysis for the association between overall survival and progression-free survival in gastrointestinal stromal tumor.

PURPOSE: Gastrointestinal stromal tumor (GIST) is a relatively rare tumor that is treated with targeted therapies in advanced stages. Randomized clinical trials (RCT) often require long follow-up and large sample sizes to evaluate overall survival (OS), the gold-standard measure of treatment efficacy. However, changes in therapy following disease progression may complicate survival assessments. Establishing surrogate endpoints may facilitate the drug approval and availability of new efficacious treatments; however, no published studies have investigated this topic in unresectable and/or metastatic GIST. EXPERIMENTAL DESIGN: A systematic literature review identified 14 RCTs and five observational studies of sufficient methodologic quality published between January 1995 and December 2013 (29 treatment arms; 2,189 patients). Weighted linear regression was used to evaluate the relation between median OS and median progression-free survival (PFS) for all arms combined and stratified by treatment line, treatment type, and quality score. RESULTS: Median OS and PFS were positively related with a correlation of 0.91. The association was still moderate (correlation 0.72) after eliminating four influential data points. In stratified analyses, correlation of OS and PFS was greater in later lines of therapy (first line = 0.52; second line = 0.80; third- and later-line = 0.70) and imatinib showed a stronger association (0.91) than other evaluated treatments (-0.26 to 0.69). CONCLUSION: This analysis identified a strong relationship between median OS and PFS, especially in later lines of therapy. Findings suggest that PFS could serve as a surrogate marker for OS; however, analyses of patient-level data are needed to establish its validity in GIST.

Cost-effectiveness analysis of tapentadol immediate release for the treatment of acute pain.

BACKGROUND: Tapentadol immediate-release (IR) tablets are indicated for the treatment of moderate to severe acute pain. In clinical trials, tapentadol IR effectively reduced moderate to severe pain with improved tolerability compared with oxycodone IR at doses providing comparable analgesia. OBJECTIVE: This analysis compared the cost-effectiveness of tapentadol IR with doses of oxycodone IR providing comparable analgesia in the outpatient treatment of acute postsurgical and nonsurgical pain. The perspective was that of a US managed care health plan as third-party payer. METHODS: A Markov model was developed to simulate clinical-economic outcomes for tapentadol IR 100 mg compared with oxycodone IR 15 mg in the treatment of acute postsurgical pain (3 days) and for tapentadol IR 50 mg compared with oxycodone IR 10 mg in the treatment of acute nonsurgical pain (10 days). The model simulated changes in pain relief; occurrence of opioid-related adverse events (AEs); opioid switching, discontinuation, and dose change; and number of quality-adjusted life-days (QALDs). Data inputs for the model were obtained from clinical trials, claims databases, surveys, Medicare fee schedules, and other published sources. Only direct costs were included. Drug costs were based on the wholesale acquisition cost. Prescription copayments were set at $5 for oxycodone IR and $25 for tapentadol IR. All costs were in 2008 US dollars. Sensitivity analyses were conducted on key model parameters. RESULTS: The cost of pain medication per patient was higher for tapentadol IR than for oxycodone IR in both the surgical pain setting ($15.23 vs $9.57, respectively) and the nonsurgical pain setting ($57.17 vs $21.31). However, this cost difference was offset by reductions in pharmacy and medical costs associated with the treatment of AEs and opioid switching/discontinuation, resulting in a lower mean treatment cost per patient for tapentadol IR 100 mg compared with oxycodone IR 15 mg in the treatment of acute surgical pain ($52.90 vs $55.99) and for tapentadol IR 50 mg compared with oxycodone IR 10 mg in the treatment of acute nonsurgical pain ($139.48 vs $144.79). Tapentadol IR also was associated with a greater mean number of treatment days with ≥30% improvement in pain intensity without opioid-related AEs compared with oxycodone IR and a greater mean number of QALDs (surgical pain: 1.73 vs 1.68; nonsurgical pain: 6.03 vs 4.92). Because both doses of tapentadol IR were dominant (ie, lower treatment costs and greater effectiveness) relative to the corresponding doses of oxycodone IR providing com- parable analgesia, incremental cost-effectiveness ratios were not calculated. CONCLUSION: The results of this model suggest that at doses providing comparable analgesia, tapentadol IR is a cost-effective alternative to oxycodone IR for the treatment of acute surgical and nonsurgical pain.